Predictive significance of FGFR4 p.G388R polymorphism in metastatic colorectal cancer patients receiving trifluridine/tipiracil (TAS-102) treatment.

BACKGROUND: TAS-102 (Lonsurf®) is an oral fluoropyrimidine consisting of a combination of trifluridine (a thymidine analog) and tipiracil (a thymidine phosphorylation inhibitor). The drug is effective in metastatic colorectal cancer (mCRC) patients refractory to fluorouracil, irinotecan and oxaliplatin. This study is a real-world analysis, investigating the interplay of genotype/phenotype in relation to TAS-102 sensitivity. METHODS: Forty-seven consecutive mCRC patients were treated with TAS-102 at the National Cancer Institute of Naples from March 2019 to March 2021, at a dosage of 35 mg/m2, twice a day, in cycles of 28 days (from day 1 to 5 and from day 8 to 12). Clinical-pathological parameters were described. Activity was evaluated with RECIST criteria (v1.1) and toxicity with NCI-CTC (v5.0). Survival was depicted through the Kaplan-Meyer curves. Genetic features of patients were evaluated with Next Generation Sequencing (NGS) through the Illumina NovaSeq 6000 platform and TruSigt™Oncology 500 kit. RESULTS: Median age of patients was 65 years (range: 46-77). Forty-one patients had 2 or more metastatic sites and 38 patients underwent to more than 2 previous lines of therapies. ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) was 2 in 19 patients. The median number of TAS-102 cycles was 4 (range: 2-12). The most frequent toxic event was neutropenia (G3/G4 in 16 patients). There were no severe (> 3) non-haematological toxicities or treatment-related deaths. Twenty-six patients experienced progressive disease (PD), 21 stable disease (SD). Three patients with long-lasting disease control (DC: complete, partial responses or stable disease) shared an FGFR4 (p.Gly388Arg) mutation. Patients experiencing DC had more frequently a low tumour growth rate (P = 0.0306) and an FGFR4 p.G388R variant (P < 0.0001). The FGFR4 Arg388 genotype was associated with better survival (median: 6.4 months) compared to the Gly388 genotype (median: 4 months); the HR was 0.25 (95% CI 0.12- 0.51; P = 0.0001 at Log-Rank test). CONCLUSIONS: This phenotype/genotype investigation suggests that the FGFR4 p.G388R variant may serve as a new marker for identifying patients who are responsive to TAS-102. A mechanistic hypothesis is proposed to interpret these findings.

An overview on multimodal imaging for the diagnostic workup of pleural mesothelioma.

Pleural mesothelioma (PM) is an aggressive disease that has a strong causal relationship with asbestos exposure and represents a major challenge from both a diagnostic and therapeutic viewpoint. Despite recent improvements in patient care, PM typically carries a poor outcome, especially in advanced stages. Therefore, a timely and effective diagnosis taking advantage of currently available imaging techniques is essential to perform an accurate staging and dictate the most appropriate treatment strategy. Our aim is to provide a brief, but exhaustive and up-to-date overview of the role of multimodal medical imaging in the management of PM.

Dose Reduction Strategies for Pregnant Women in Emergency Settings.

In modern clinical practice, there is an increasing dependence on imaging techniques in several settings, and especially during emergencies. Consequently, there has been an increase in the frequency of imaging examinations and thus also an increased risk of radiation exposure. In this context, a critical phase is a woman's pregnancy management that requires a proper diagnostic assessment to reduce radiation risk to the fetus and mother. The risk is greatest during the first phases of pregnancy at the time of organogenesis. Therefore, the principles of radiation protection should guide the multidisciplinary team. Although diagnostic tools that do not employ ionizing radiation, such as ultrasound (US) and magnetic resonance imaging (MRI) should be preferred, in several settings as polytrauma, computed tomography (CT) nonetheless remains the examination to perform, beyond the fetus risk. In addition, protocol optimization, using dose-limiting protocols and avoiding multiple acquisitions, is a critical point that makes it possible to reduce risks. The purpose of this review is to provide a critical evaluation of emergency conditions, e.g., abdominal pain and trauma, considering the different diagnostic tools that should be used as study protocols in order to control the dose to the pregnant woman and fetus.

Oligo-Metastatic Cancers: Putative Biomarkers, Emerging Challenges and New Perspectives.

Some cancer patients display a less aggressive form of metastatic disease, characterized by a low tumor burden and involving a smaller number of sites, which is referred to as "oligometastatic disease" (OMD). This review discusses new biomarkers, as well as methodological challenges and perspectives characterizing OMD. Recent studies have revealed that specific microRNA profiles, chromosome patterns, driver gene mutations (ERBB2, PBRM1, SETD2, KRAS, PIK3CA, SMAD4), polymorphisms (TCF7L2), and levels of immune cell infiltration into metastases, depending on the tumor type, are associated with an oligometastatic behavior. This suggests that OMD could be a distinct disease with specific biological and molecular characteristics. Therefore, the heterogeneity of initial tumor burden and inclusion of OMD patients in clinical trials pose a crucial methodological question that requires responses in the near future. Additionally, a solid understanding of the molecular and biological features of OMD will be necessary to support and complete the clinical staging systems, enabling a better distinction of metastatic behavior and tailored treatments.

Radiation Recall Pneumonitis: The Open Challenge in Differential Diagnosis of Pneumonia Induced by Oncological Treatments.

The treatment of primary and secondary lung neoplasms now sees the fundamental role of radiotherapy, associated with surgery and systemic therapies. The improvement in survival outcomes has also increased attention to the quality of life, treatment compliance and the management of side effects. The role of imaging is not only limited to recognizing the efficacy of treatment but also to identifying, as soon as possible, the uncommon effects, especially when more treatments, such as chemotherapy, immunotherapy and radiotherapy, are associated. Radiation recall pneumonitis is an uncommon treatment complication that should be correctly characterized, and it is essential to recognize the mechanisms of radiation recall pneumonitis pathogenesis and diagnostic features in order to promptly identify them and adopt the best therapeutic strategy, with the shortest possible withdrawal of the current oncological drug. In this setting, artificial intelligence could have a critical role, although a larger patient data set is required.

Immunotherapy Assessment: A New Paradigm for Radiologists.

Immunotherapy denotes an exemplar change in an oncological setting. Despite the effective application of these treatments across a broad range of tumors, only a minority of patients have beneficial effects. The efficacy of immunotherapy is affected by several factors, including human immunity, which is strongly correlated to genetic features, such as intra-tumor heterogeneity. Classic imaging assessment, based on computed tomography (CT) or magnetic resonance imaging (MRI), which is useful for conventional treatments, has a limited role in immunotherapy. The reason is due to different patterns of response and/or progression during this kind of treatment which differs from those seen during other treatments, such as the possibility to assess the wide spectrum of immunotherapy-correlated toxic effects (ir-AEs) as soon as possible. In addition, considering the unusual response patterns, the limits of conventional response criteria and the necessity of using related immune-response criteria are clear. Radiomics analysis is a recent field of great interest in a radiological setting and recently it has grown the idea that we could identify patients who will be fit for this treatment or who will develop ir-AEs.

Risk Management Activities in a Lung Cancer Multidisciplinary Team at a Comprehensive Cancer Center: Results of a Prospective Analysis.

PURPOSE: The objective of the study was to highlight sources of harm that could negatively affect the lung cancer multidisciplinary team (MDT) activities to reduce the level of risk of each factor. METHODS: A modified Delphi approach was used by a board of multi-health care professionals of the lung cancer MDT to identify the main processes, subprocesses, and risk factors of the multidisciplinary pathway of patients with lung cancer. A semiquantitative matrix was built with a five-point scale for probability of harm (likelihood) and severity of harm (consequences) according to the international risk management standards (ISO 31000-2018). The risk level was calculated by multiplying likelihood × consequences. Mitigation strategies have been identified and applied by the MDT to reduce risks to acceptable levels. RESULTS: Three main processes (outpatient specialist visit, MDT discussion, and MDT program implementation), eight related subprocesses, and 16 risk factors were identified. Four risk factors (25%) were related to outpatient specialist visit, seven (43.75%) to case discussion, and five (31.25%) to program implementation. Overall, two risk factors were assigned a low-risk level (12.5%), 11 a moderate-risk level (68.75%), one (6.25%) a high-risk level, and two (12.5%) a very high-risk level. After the implementation of mitigation measures, the new semiquantitative risk analysis showed a reduction in almost all hazardous situations: two risk factors (12.5%) were given a very low level, six (37.5%) a low level, seven (43.75%) a moderate level, and one (6.25%) a very high level. CONCLUSION: An interdisciplinary risk assessment analysis is applicable to MDT activities by using an ad hoc risk matrix: if the hazard is identified and monitored, the risk could be reduced and managed in a short time.

Genetic landscape of colorectal cancer patients manifesting tumor shrinkage during SARS-Cov-2 infection.

We previously described three patients affected by metastatic colorectal cancer (mCRC) who experienced spontaneous tumour shrinkage during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thereafter, the patients were closely monitored and no systemic treatments were applied. Here, we report follow-up clinical information about these patients as well as genetic characterization of their primary tumours through the TruSigt™Oncology 500 Next Generation Sequencing test targeting 523 cancer-relevant genes. An Illumina NovaSeq 6000 platform was used to perform sequencing. Time-to-progression was 23 and 2 months, respectively, in Patients 2 and 3 while it was not reached in Patient 1. Patients 1 and 2 had the greatest anti-SARS-CoV-2 IgG titres. Assessment of genetic landscapes evidenced common mutation in BARD1 gene (p.Val507Met) in Patients 1 and 2. Although our report is descriptive in its nature, we suggest that complex and unexplored interactions between genetic background and components of the immune response to SARS-CoV-2 infection could be responsible of unexpected rare mCRC shrinkage.

Lurbinectedin in small cell lung cancer.

Few treatment options are available for patients with small cell lung cancer (SCLC) in progression after a first-line therapy. A novel therapeutic approach is represented by lurbinectedin, a synthetic derivative of trabectedin that works by inhibiting oncogenic transcription and promoting apoptosis in tumor cells. A phase II basket trial demonstrated the activity of lurbinectedin at the dose of 3.2 mg/m2 in patients with SCLC who had failed a previous chemotherapy, with a response rate of 35.2%, a median progression-free survival (mPFS) of 3.5 months, and a median overall survival (mOS) of 9.3 months. Common severe adverse events (grades 3-4) were hematological disorders, including anemia (9%), leukopenia (29%), neutropenia (46%), and thrombocytopenia (7%). On the basis of the positive results of this phase II study, on June 2020, lurbinectedin was approved by the Food and Drug Administration as second line for SCLC patients in progression on or after platinum-based therapy. The subsequent phase III trial comparing the combination of lurbinectedin plus doxorubicin vs. CAV (cyclophosphamide, Adriamycin, and vincristine) or topotecan did not demonstrate an improvement in overall survival, although the experimental arm showed a superior safety profile. Combinations of lurbinectedin with other drugs, cytotoxic agents and immune checkpoint inhibitors, are currently under investigation. The results of these studies should better define the optimal clinical application of lurbinectedin.

Imaging Assessment of Interval Metastasis from Melanoma.

Interval metastasis is a particular metastatic category of metastatic localizations in the lymph nodes in patients with melanoma. Interval nodes are generally located at nonregional lymphatic stations placed along the pathway of the spread of melanoma, such as the epitrochlear lymph node station, the popliteal fossa, and the retroareolar station. Imaging techniques for evaluation of patients with interval metastasis from melanoma diseases include ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), lymphoscintigraphy (LS), and positron emission tomography (PET). A literature review was conducted through a methodical search on the Pubmed and Embase databases. The evaluation of lymph node metastases represents a critical phase in the staging and follow-up of melanoma patients. Therefore, a thorough knowledge of the imaging methods available and the interactions between the clinician and the radiologist are essential for making the correct choice for individual patients, for a better management, and to improve treatment and survival.

Multimodality Imaging Assessment of Desmoid Tumors: The Great Mime in the Era of Multidisciplinary Teams.

Desmoid tumors (DTs), also known as desmoid fibromatosis or aggressive fibromatosis, are rare, locally invasive, non-metastatic soft tissue tumors. Although histological results represent the gold standard diagnosis, imaging represents the fundamental tool for the diagnosis of these tumors. Although histological analysis represents the gold standard for diagnosis, imaging represents the fundamental tool for the diagnosis of these tumors. DTs represent a challenge for the radiologist, being able to mimic different pathological conditions. A proper diagnosis is required to establish an adequate therapeutic approach. Multimodality imaging, including ultrasound (US), computed tomography (CT) and Magnetic Resonance Imaging (MRI), should be preferred. Different imaging techniques can also guide minimally invasive treatments and monitor their effectiveness. The purpose of this review is to describe the state-of-the-art multidisciplinary imaging of DTs; and its role in patient management.

Not only lymphadenopathy: case of chest lymphangitis assessed with MRI after COVID 19 vaccine.

BACKGROUND: To date, no paper reports cases of lymphangitis after COVID 19 vaccination. We present a case of lymphangitis after vaccination from COVID 19, in a patient with colorectal liver metastases. METHODS: We described the case of a 56-year-old woman with history of a surgical resection of colorectal cancer and liver metastases, without any kind of drug therapy for about a month. In addition, a recent administration (2 days ago) of Spikevax (mRNA-1273, Moderna vaccine), as a booster dose, on the right arm was reported. RESULTS: The magnetic resonance (MR) examination showed the effects of the previous surgical resection and five new hepatic metastases, located in the VIII, VI, V, IV and II hepatic segments. As an accessory finding the presence of lymphadenopathy in the axillary area and lymphangitis of the right breast and chest were identified. The computed tomography scan performed a week earlier, and re-evaluated in light of the MR data, did not identify the presence of lymphadenopathy in the axillary area and lymphangitis signs. CONCLUSIONS: Lymphangitis could occur after COVID 19 vaccine and it is important to know this data to avoid alarmism in patients and clinicians and economic waste linked to the execution of various radiological investigations for the search for a tumour that probably does not exist. TRIAL REGISTRATION: Not applicable.

Liquid Biopsy Testing for the Management of Patient with Non-Small Cell Lung Cancer Carrying a Rare Exon-20 EGFR Insertion.

Increasing evidence suggests that liquid biopsy might play a relevant role in the management of metastatic non-small cell lung cancer (NSCLC) patients. Here, we show how the Molecular Tumor Board (MTB) in our cancer center employed liquid biopsy to support therapeutic decisions in a patient with NSCLC carrying a rare EGFR mutation. A 44-year-old woman, never-smoker with an EGFR, ALK, and ROS1-negative lung adenocarcinoma and multiple brain metastases received systemic therapy and surgery before being referred to our Institute. The MTB suggested NGS testing of tumor biopsy that revealed a rare exon-20 EGFR insertion (p.His773dup; c.2315_2316insCCA) and EGFR amplification. The MTB recommended treatment with erlotinib and follow-up with liquid biopsy, by using both cell-free DNA (cfDNA) and circulating tumor cells (CTCs). An increase of EGFR mutation levels in cfDNA revealed resistance to treatment about 6 months before clinical progression. Extremely low levels of EGFR p.T790M were detected at progression. Based on preclinical data suggesting activity of osimertinib against EGFR exon-20 insertions, the MTB recommended treatment with brain and bone radiotherapy and osimertinib. A dramatic reduction of EGFR mutation levels in the cfDNA was observed after 4 weeks of treatment. The PET scan demonstrated a metabolic partial remission that was maintained for 9 months. This case supports the evidence that liquid biopsy can aid in the management of metastatic NSCLC. It also suggests that treatment with osimertinib might be a therapeutic option in patients with EGFR exon-20 insertions when a clinical trial is not available.

RET Inhibitors in Non-Small-Cell Lung Cancer.

RET rearrangements are observed in 1-2% of non-small-cell lung cancer (NSCLC) patients and result in the constitutive activation of downstream pathways normally implied in cell proliferation, growth, differentiation and survival. In NSCLC patients, RET rearrangements have been associated with a history of non-smoking, a higher rate of brain metastasis at initial diagnosis and a low immune infiltrate. Traditionally, RET fusions are considered mutually exclusive with other oncogenic drivers, even though a co-occurrence with EGFR mutations and MET amplifications has been observed. Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.

Evolution of CT Findings and Lung Residue in Patients with COVID-19 Pneumonia: Quantitative Analysis of the Disease with a Computer Automatic Tool.

PURPOSE: the purpose of this study was to assess the evolution of computed tomography (CT) findings and lung residue in patients with COVID-19 pneumonia, via quantified evaluation of the disease, using a computer aided tool. MATERIALS AND METHODS: we retrospectively evaluated 341 CT examinations of 140 patients (68 years of median age) infected with COVID-19 (confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR)), who were hospitalized, and who received clinical and CT examinations. All CTs were evaluated by two expert radiologists, in consensus, at the same reading session, using a computer-aided tool for quantification of the pulmonary disease. The parameters obtained using the computer tool included the healthy residual parenchyma, ground glass opacity, consolidation, and total lung volume. RESULTS: statistically significant differences (p value ≤ 0.05) were found among quantified volumes of healthy residual parenchyma, ground glass opacity (GGO), consolidation, and total lung volume, considering different clinical conditions (stable, improved, and worsened). Statistically significant differences were found among quantified volumes for healthy residual parenchyma, GGO, and consolidation (p value ≤ 0.05) between dead patients and discharged patients. CT was not performed on cadavers; the death was an outcome, which was retrospectively included to differentiate findings of patients who survived vs. patients who died during hospitalization. Among discharged patients, complete disease resolutions on CT scans were observed in 62/129 patients with lung disease involvement ≤5%; lung disease involvement from 5% to 15% was found in 40/129 patients, while 27/129 patients had lung disease involvement between 16 and 30%. Moreover, 8-21 days (after hospital admission) was an "advanced period" with the most severe lung disease involvement. After the extent of involvement started to decrease-particularly after 21 days-the absorption was more obvious. CONCLUSIONS: a complete disease resolution on chest CT scans was observed in 48.1% of discharged patients using a computer-aided tool to quantify the GGO and consolidation volumes; after 16 days of hospital admission, the abnormalities identified by chest CT began to improve; in particular, the absorption was more obvious after 21 days.

Preliminary Report on Computed Tomography Radiomics Features as Biomarkers to Immunotherapy Selection in Lung Adenocarcinoma Patients.

PURPOSE: To assess the efficacy of radiomics features obtained by computed tomography (CT) examination as biomarkers in order to select patients with lung adenocarcinoma who would benefit from immunotherapy. METHODS: Seventy-four patients (median age 63 years, range 42-86 years) with histologically confirmed lung cancer who underwent immunotherapy as first- or second-line therapy and who had baseline CT studies were enrolled in this approved retrospective study. As a control group, we selected 50 patients (median age 66 years, range 36-86 years) from 2005 to 2013 with histologically confirmed lung adenocarcinoma who underwent chemotherapy alone or in combination with targeted therapy. A total of 573 radiomic metrics were extracted: 14 features based on Hounsfield unit values specific for lung CT images; 66 first-order profile features based on intensity values; 43 second-order profile features based on lesion shape; 393 third-order profile features; and 57 features with higher-order profiles. Univariate and multivariate statistical analysis with pattern recognition approaches and the least absolute shrinkage and selection operator (LASSO) method were used to assess the capability of extracted radiomics features to predict overall survival (OS) and progression free survival (PFS) time. RESULTS: A total of 38 patients (median age 61; range 41-78 years) with confirmed lung adenocarcinoma and subjected to immunotherapy satisfied inclusion criteria, and 50 patients in a control group were included in the analysis The shift in the center of mass of the lesion due to image intensity was significant both to predict OS in patients subjected to immunotherapy and to predict PFS in patients subjected to immunotherapy and in patients in the control group. With univariate analysis, low diagnostic accuracy was reached to stratify patients based on OS and PFS time. Regarding multivariate analysis, considering the robust (two morphological features, three textural features and three higher-order statistical metrics) application of the LASSO approach and all patients, a support vector machine reached the best results for stratifying patients based on OS (area under curve (AUC) of 0.89 and accuracy of 81.6%). Alternatively, considering the robust predictors (six textural features and one higher-order statistical metric) and application of the LASSO approach including all patients, a decision tree reached the best results for stratifying patients based on PFS time (AUC of 0.96 and accuracy of 94.7%). CONCLUSIONS: Specific radiomic features could be used to select patients with lung adenocarcinoma who would benefit from immunotherapy because a subset of imaging radiomic features useful to predict OS or PFS time were different between the control group and the immunotherapy group.

Radiomics in hepatic metastasis by colorectal cancer.

BACKGROUND: Radiomics is an emerging field and has a keen interest, especially in the oncology field. The process of a radiomics study consists of lesion segmentation, feature extraction, consistency analysis of features, feature selection, and model building. Manual segmentation is one of the most critical parts of radiomics. It can be time-consuming and suffers from variability in tumor delineation, which leads to the reproducibility problem of calculating parameters and assessing spatial tumor heterogeneity, particularly in large or multiple tumors. Radiomic features provides data on tumor phenotype as well as cancer microenvironment. Radiomics derived parameters, when associated with other pertinent data and correlated with outcomes data, can produce accurate robust evidence based clinical decision support systems. The principal challenge is the optimal collection and integration of diverse multimodal data sources in a quantitative manner that delivers unambiguous clinical predictions that accurately and robustly enable outcome prediction as a function of the impending decisions. METHODS: The search covered the years from January 2010 to January 2021. The inclusion criterion was: clinical study evaluating radiomics of liver colorectal metastases. Exclusion criteria were studies with no sufficient reported data, case report, review or editorial letter. RESULTS: We recognized 38 studies that assessed radiomics in mCRC from January 2010 to January 2021. Twenty were on different tpics, 5 corresponded to most criteria; 3 are review, or letter to editors; so 10 articles were included. CONCLUSIONS: In colorectal liver metastases radiomics should be a valid tool for the characterization of lesions, in the stratification of patients based on the risk of relapse after surgical treatment and in the prediction of response to chemotherapy treatment.

Unexpected tumor reduction in metastatic colorectal cancer patients during SARS-Cov-2 infection.

Herein, we describe three patients affected by metastatic colorectal cancer (mCRC) experiencing infection by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and reduction of disease burden during coronavirus disease 2019 (COVID-19) course. Insights into tumor-associated angiotensin-converting enzyme (ACE)-2 expression and lymphocyte function suggest a correlation between host/SARS-Cov-2 infection and tumor burden reduction. This may shed new light into (a) the infection mechanism of SARS-CoV-2 virus and (b) the multiple aspects of a composite antiviral immune response with potential paradoxical and unexpected applications.

Aflibercept or bevacizumab in combination with FOLFIRI as second-line treatment of mRAS metastatic colorectal cancer patients: the ARBITRATION study protocol.

BACKGROUND: The intensive study of predictive factors has strongly ameliorated the therapeutic flow-chart of metastatic colorectal cancer (mCRC) by allowing the selection of patients who benefit from specific therapies. For instance, in mRAS (mutated RAS) mCRC patients, anti-EGFR drugs (cetuximab and panitumumab) are not recommended; in this group of patients, the use of anti-angiogenic drugs (bevacizumab and aflibercept) is predominant. However, at progression to standard bevacizumab-based first-line chemotherapy, still to date, there are no studies to guide oncologists in the choice of the best second-line anti-angiogenic drug (bevacizumab beyond progression versus aflibercept). METHODS: ARBITRATION is a prospective, observational study assessing efficacy differences between second-line fluorouracil/irinotecan (FOLFIRI)/bevacizumab versus FOLFIRI/aflibercept at progression to fluoropyrimidines, oxaliplatin and bevacizumab in mRAS mCRC patients. A test power of 80%, a median survival of 9 months from second-line treatment start and a hazard ratio of 0.67 between the two schedules were the basis for statistical design. The final sample will be 220 patients (110 per treatment). The significance will be verified with a two-tailed log-rank test with an alpha value of the I-type error of 5%. Time-to-outcome will be described by Kaplan-Meier curves and prognostic factors studied through multivariable analyses based on the Cox model. Secondary objectives include safety, responses' duration and progression-free survival. A translational research will be conducted to measure several angiogenic proteins in patients' serum before starting the therapy in order to evidence any angiogenic factor patterns related to outcome. DISCUSSION: We present a large, prospective, observational study aiming to answer two scientific questions: (1) outcome differences between second-line treatments with FOLFIRI/bevacizumab beyond progression versus FOLFIRI/aflibercept in mRAS mCRC patients, (2) angiogenic factors' patterns that could associate with efficacy and help oncologists to apply best the therapeutic anti-angiogenic strategies. TRIAL REGISTRATION: The ARBITRATION trial (version 0.0, 13 April 2020) has been registered into the clinicaltrials.gov registry on 20 May 2020 with identifier NCT04397601.

Lymphadenopathy after BNT162b2 Covid-19 Vaccine: Preliminary Ultrasound Findings.

During a spontaneous and autonomous study, we assessed the ultrasound finding of lymphadenopathy after BNT162b2 Pfizer vaccine. We enrolled 18 patients with 58 lymphadenopathies: in 10 patients, they were in the laterocervical side, while in 8 patients in the axillar site. The largest diameter was 16 mm with a range from 7 to 16 mm (median value = 10 mm). In the same patient, we found different ultrasound nodal findings. A total of 25 nodes showed eccentric cortical thickening with wide echogenic hilum and oval shape. In total, 19 nodes showed asymmetric eccentric cortical thickening with wide echogenic hilum and oval shape. Overall, 10 nodes showed concentric cortical thickening with reduction in the width of the echogenic hilum and oval shape. A total of four nodes showed huge reduction and displacement of the echogenic hilum and round or oval shape. No anomaly was found at the Doppler echocolor study. In conclusion, eccentric cortical thickening with wide echogenic hilum and oval shape, asymmetric eccentric cortical thickening with wide echogenic hilum and oval shape, concentric cortical thickening with reduction in the width of the echogenic hilum and oval shape, and a huge reduction and displacement of the echogenic hilum and round shape are the features that we found in post BNT162b2 Covid-19 Vaccine lymphadenopathies.